title: Identification of Dermcidin as a novel binding protein of Nck1 and characterization of its role in promoting cell migration.
abstract: A distinct feature of hepatocellular carcinoma (HCC) is the tendency of tumor cells to disperse throughout the liver. Nck family adaptor proteins function to couple tyrosine phosphorylation signals to regulate actin cytoskeletal reorganization that leads to cell motility. In order to explore the role of Nck in HCC development, we performed GST pull-down assay using the SH2 domain of Nck1 as bait. The resulting precipitates were separated by 2-DE. Mass spectrometry analysis revealed a group of Nck1 SH2 domain-binding proteins that were differentially expressed in HCC. One of these proteins, dermcidin (DCD), and its interaction with Nck1, was further validated in vitro. GST pull-down assay revealed that Nck1 SH2 domain binds to the phosphotyrosine residue at position 20 (Y20) of the DCD. Pervandate treatment significantly enhanced the interaction between DCD and Nck1. Moreover, we demonstrated that forced expression of DCD could activate Rac1 and Cdc42 and promoted cell migration. Taken together, these data suggest a role of DCD in tumor metastasis.
authors.affiliation: Department of Hepatobiliary Surgery, The First Affiliated Hospital of Sun Yat-sen University, Guangzhou, PR China.
authors.forename: Shun-Li
authors.initials: SL
authors.lastname: Shen
authors.forename: Fang-Hua
authors.initials: FH
authors.lastname: Qiu
authors.forename: Thamara K
authors.initials: TK
authors.lastname: Dayarathna
authors.forename: Jian
authors.initials: J
authors.lastname: Wu
authors.forename: Ming
authors.initials: M
authors.lastname: Kuang
authors.forename: Shawn S-C
authors.initials: SS
authors.lastname: Li
authors.forename: Bao-Gang
authors.initials: BG
authors.lastname: Peng
authors.forename: Jing
authors.initials: J
authors.lastname: Nie
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000378:metabolism*; D000328:Adult; D000368:Aged; D006528:Carcinoma, Hepatocellular / Q000737:chemistry / Q000473:pathology*; D045744:Cell Line, Tumor; D002465:Cell Movement; D005260:Female; D006801:Humans; D008099:Liver / Q000737:chemistry; D008113:Liver Neoplasms / Q000737:chemistry / Q000473:pathology*; D008297:Male; D008875:Middle Aged; D015513:Oncogene Proteins / Q000378:metabolism*; D010455:Peptides / Q000032:analysis / Q000502:physiology*; D010766:Phosphorylation; D011485:Protein Binding; D040901:Proteomics; D014443:Tyrosine / Q000378:metabolism; D020741:rho GTP-Binding Proteins / Q000502:physiology; D018909:src Homology Domains
chemical_list: D048868:Adaptor Proteins, Signal Transducing; C078332:Nck protein; D015513:Oncogene Proteins; D010455:Peptides; C442243:dermcidin; D014443:Tyrosine; D020741:rho GTP-Binding Proteins